Compositions and methods containing high purity fatty alcohol C24 to C36 for cosmetic applications

ABSTRACT

The present invention discloses the cosmetic applications of alkylalkanols collectively referred to as policosanol, for control of sebum secretion, as anti-acne component and as emollient.

CROSS REFERENCE TO EXISTING APPLICATION

This application is a divisional application of U.S. patent applicationSer. No. 10/604,203 titled “Commercially viable process for high purityof fatty alcohol C24 to C36 and its cosmetic application for skin hairand nails” filed on Jul. 1, 2003.

BACKGROUND OF THE INVENTION

Policosanol is a natural mixture of higher aliphatic primary alcohols(C24-C36) isolated from sugarcane wax and beeswax. It contains1-Octacosanol, Triacontanol, Tetracosanol, Hexacosanol, Heptacosanol.These C₂₄ to C₃₆ primary alcohols are also found in sugarcane wax,ricebran wax, beeswax and various vegetable wax.

The structures of these primary alkanols are shown below. C₂₄Tetracosanol CH₃(CH₂)₂₂CH₂OH C₂₆ Hexacosanol CH₃(CH₂)₂₄CH₂OH C₂₈Octacosanol CH₃(CH₂)₂₆CH₂OH C₃₀ Triacontanol CH₃(CH₂)₂₈CH₂OH C₃₆Tetratriacontanol CH₃(CH₂)₃₂CH₂OH C₂₇ Heptacosanol CH₃(CH₂)₂₅CH₂OH

-   C₂₄ Tetracosanol CH₃ (CH₂)₂₂CH₂OH-   C₂₆ Hexacosanol CH₃ (CH₂)₂₄CH₂OH-   C₂₈ Octacosanol CH₃ (CH₂)₂₆CH₂OH-   C₃₀ Triacontanol CH₃ (CH₂)₂₈CH₂OH-   C₃₆ Tetratriacontanol CH₃ (CH₂)₃₂CH₂OH-   C₂₇ Heptacosanol CH₃ (CH₂)₂₅CH₂OH

Evaluation of Policosanol on Sebum Levels in Human Volunteers

Study Methodology and Administration

Sixteen healthy males of between 18 and 25 years of age were included inthe study after they had signed the informed consent form. The maininclusion criterion was those with oily skin (scores >4 on a 0-5 scale).All the subjects were required to abstain from taking drugs, applyingcosmetic products to their skin and exposing themselves to sunlight orany other source of ultraviolet radiation throughout the duration of thestudy.

2% or 5% Policosanol colloidal solution in 1,2 hexanediol was applied(0.2 ml) for seven days, twice daily, on the forehead. One side offorehead being treatment and the other side being the control (1,2hexanediol treatment).

The efficacy was evaluated based on self-assessment and on theassessment of a panel of five independent cosmetologists, visually,using Sebutape (CuDerm Corp., Dallas, Tex.).

The sebutape is made of microporous, hydrophobic polymeric film composedof many tiny air cavities. The surface of the film is coated with alipid porous adhesive layer that enables the tape to adhere to the skinsurface. The tape is applied to the skin test site for optimal period of1 hr. Sebum is absorbed into the tape, displacing the air in themicrocavities. As this occurs, the lipid-filled cavities becometransparent to light. Through this process, the sebum output from eachfollicle forms a sharply defined clear spot, its size roughlycorresponding to the sebum volume.

When the sebutape are placed on the black background of the score card,the sebum on the tape becomes clearly visible as black spots. Thesespots are scored by a panel of cosmetologists on a scale of 0-5. Theseare pooled and from the mean of the scores, the percentage change iscalculated from the control treatment site.

The safety and adverse events like erythema, burning sensation, itching,urticaria, edema, dermatitis, ochronosis, dryness of skin and any othernon specific reactions, if any, were monitored.

The Policosanol colloidal solution was applied twice a day on one sideof the forehead area for seven days. Pre-cleansing with soap/water wasdone before applications. The following observations were made

2% and 5% Policosanol colloidal solution was found to be safe for localapplication. It did not show any significant side effects and is safefor use on skin

Topical application of the Policosanol colloidal solution was found todecrease the sebum secretion in a concentration dependent manner. The 2%Policosanol solution reduced the sebum levels by about 11%, while 5%solution reduced sebum secretion by 27%.

Both the self-assessment and the assessment by the panel ofcosmetologist revealed that 100% of the subjects showed marked decreasein sebum release.

The colloidal solution was found to be effective in people withmoderately high oily skin (scores >3.5).

Additionally, one surprising observation was that Policosanol treatmentprotected the 1,2 Hexanediol induced dryness of skin and made the skinsmooth and soft. TABLE 1 Effect of Policosanol on the sebum secretion inhuman volunteers Sebum secretion Percentage (Mean Scores of reduction ofsebutape by a five sebum Groups member panel) release Control  4.2 +0.49 — 2% 3.71 + 0.41 11.6%   Policosanol (n = 8) 5% 3.29 + 0.3327.66%   Policosanol (n = 8)

Anti-microbial Study against Propionibacterium acnes

To carry out the antibacterial activity of the products against Pr.acnes, the organism was first cultured in the anaerobic environment forwhich the anaerobic chamber was used. To standardize the growth ofanaerobic culture of Pr. acnes in the anaerobic chamber, differentculture media were used.

The anaerobic chamber [Model 8301-230, 3 ft polymer] used in the studywas purchased from COY LABORATORY, USA which is provided with anautomatic Air lock purge system.

The anaerobic condition in the chamber was maintained by initializationwith N₂ gas and then the mixture of gases of N₂+H₂+CO₂ in the proportion80+10+10. Two gas tank arrangement was made wherein only N₂ wasconnected to the transfer chamber and mixed gas to the main chamberusing Gassing Manifold (Hrishi Biotech, Pune, India)

Preparation of Anaerobic Media

The anaerobic media were prepared by heating the media while passing themixture of gases of N₂ and CO₂ in 4:1 proportion simultaneously. Themedia were added with a redox indicator [resazurin: 0.001%] which iscolorless in the presence of anaerobiasis and shows blue color in itsabsence. It was dispensed to 30/20/10 ml vials and sealed with rubbersand aluminum clamps and sterilized by autoclaving at 121° C. for minutes

Antimicrobial Study

Preparation of the inoculum The culture used in the study isPropionibacterium acnes ATCC 11827. The culture from the broth wasinoculated to the fresh medium in vials (10%) and incubated for 48 hoursat 37° C. The optical density (OD) of the culture at 625 nm wasmeasured. It was maintained between 0.64 and 0.80 which containsapproximately 12×10⁶ cells/ml [4.0 MC Farland standard]

Procedure

Medium used for this study was reinforced clostridial agar (RCA). Themedium that was prepared and sterilized in 30-ml vials was poured intothe plates inside the chamber and allowed to solidify.

The culture was inoculated [0.3 ml/plate] into the plates and spread.After 30 minutes, antibacterial sterile discs [6 mm] were dispensed(2/plate). 2.5, 5.0, 7.5 and 10 μl of the prepared samples and controlswere dispensed onto the discs. The plates were incubated inside theanaerobic chamber at 37° C. for 48 hours duration.

Policosanol in different concentrations (0.1-2%) prepared in 1,2Hexanediol was used as vehicle for the study with 1,2 Hexanediol ascontrol. Clindac A (Clindamycin Phosphate Gel 1% w/w) was used aspositive control. The clearance zone formed around the discs weremeasured and expressed in mm. The results of the study are given belowConc. of the Zone of inhibition sample (in mm) SI. No. (%) PolicosanolClindamycin 1 2.0 12.0 11.0 2 1.5 9.0 9.0 3 1.0 8.0 8.0 4 0.5 0.0 0.0 50.01 0.0 0.0

As seen in the results above, Policosanol is effectively inhibitingPropionibacterium acnes in concentrations above 1% and the activity iscomparable with Clindamycin gel. Inhibition of anaerobic organismscoupled with decrease in sebum secretion complements to its use incosmetic formulations to control acne, as anti-seborrhea andantimicrobial, additionally could provide moisturizing properties.Policosanol could be used alone or in combination with otherantibacterial, blemish erasers, sunscreen boosters amongst others.

Cosmetic Formulations based on Policosanol are described in thefollowing examples.

EXAMPLE 3 Sebum Control Anti-acne Cream

Percentage Actives Boswellin CG 0.2 Policosanol 1.0 Coleus oil 2.0 Vit E1.0 THP 0.1 Passives Cetyl Alcohol 4.0 Glyceryl monostearate 3.0Cetostearyl alcohol 3.0 Isopropyl myristate 2.0 Myristyl myristate 1.0Light liquid paraffin 5.0 Cetyl palmitate 1.0 BHT 1.0 BHA 0.5 CM-10002.0 Glycerin 2.0 EDTA tetra sodium 0.02 DM Water 71.0 MPS 0.2 PPS 0.02ImidUrea 0.15

EXAMPLE 4 Sebum Control Sunscreen Cream

Percentage Actives Tetrahydrocurcuminoids 0.2 Vit E 0.5 Policosanol 1.5Ethyl P-methoxy cinnamate 5.0 Avobenzone 2.0 Passives Cetyl Alcohol 2.0Glyceryl monostearate 3.0 Cetostearyl alcohol 1.0 Isopropyl myristate2.0 Spermaceti wax 2.0 Myristyl myristate 2.0 Stearic acid 5.0 PGDCC 1.5Olive oil/Almond oil 1.0 Cetyl Palmitate 1.0 BHT 0.2 BHA 0.02 Glycerin3.0 EDTA tetra sodium 0.02 DM Water 67.0 Xylosin 0.6 MPS 0.2 PPS 0.02Imidurea 0.15

EXAMPLE 5 Sebum Control Moisturizing Complex

Percentage Actives Xyloglucan 0.15 Umbelliferin 2.0 Vit E 1.0Policosanol 1.5 Almond Oil 1.0 Passives Cetyl Alcohol 4.0 Spermaceti Wax4.0 Squalene 3.0 Isopropyl myristate 3.0 Myristyl myristate 3.0 StearylStearate 1.0 Cetyl palmitate 1.0 BHT 1.0 BHA 0.01 Glyceryl Mono Stearate4.0 MCT Oil 2.0 Glycerin 3.0 Carbopol 0.18 EDTA tetra sodium 0.02 DMWater QS MPS 0.2 PPS 0.01 Imidurea 0.15 Sodium Alginate 0.13 Perfume0.40

EXAMPLE 6 Anti-dandruff, Anti-seborrhic, Hair Oil

Percentage Actives Brahmi (oil extract) 6.63 Neem oil limonoids 0.15 VitE 0.2 Policosanol 0.5 Rosmarinic acid (98%) 0.35 Passives Lauriforte 3.0Medium chain triglycerides 10.0 Isopropyl myristate 79.0 BHT 0.05Perfume 0.3

1. A composition for topical treatment of acne comprising 0.05-10% w/wof policosanol formulated with suitable carriers.
 2. A composition fortopical application to control sebum secretion in the skin or the scalpcomprising 0.05-10% policosanol formulated with suitable carriers.
 3. Acomposition for use as topical emollient in the treatment of dry skinconditions comprising 0.05-10% policosanol formulated with suitablecarriers.
 4. A composition as in claim 1 which additionally contains oneof more natural extracts selected from the group consisting of Boswelliaserrata extract, Coleus forskohlii oil, Vitex agnus-castus oil, Indiandate extract, tetrahydrocurcuminoids, tocopherols, Kaempferia galangaextract, Terminalia belerica extract, garcinol.
 5. A composition as inclaim 2 which additionally contains one or more natural extractsselected from the group consisting of Bacopa monniera extract, Indiandate extract, Vitex agnus-castus oil, Terminalia belerica extract,garcinol, Azadirachta indica extract, rosmarinic acid.
 6. A compositionas in claim 3 which additionally contains one or more natural extractsselected from the group consisting of coriander seed oil, avacado oil,sandal seed oil, xyloglucans, beta-glycans.